Personalised approaches to improve tuberculosis care:Cutting tuberculosis’ many coats according to specific cloths

Tuberculosis (TB) is an infectious disease which records 1 to 1.5 million deaths every year. Persons affected by TB have increased mortality and morbidity, despite advances made in treatment options. This thesis investigated several avenues which could enhance TB clinical care. These avenues include digital health, therapeutic drug monitoring (TDM), interventions geared towards enhancing quality of life, and enhancing policies concerning TB screening and prevention. Concerning digital health, results presented in the thesis indicate that it could be a cost-effective, feasible, and welcomed addition by both medical professionals and persons suffering from TB, to standard of care in multiple steps of the TB care cascade, from screening, to follow up. Concerning TDM, which is a personalised medicine technique informing clinicians of accurate drug dosages (usually) in blood, an international survey described in the thesis indicates that worldwide experts would recommend integrating this technique in standard of care and a retrospective study presents, in a contextualised manner, which patients would best benefit from this technique. This thesis, furthermore, presents an observational study on persons with TB quality of life and wellbeing, in order to quantify the magnitude of effects of TB during, but also after treatment completion so that future interventions could have this crucial human aspect in mind. Last, but not least, part of this thesis research focused on vulnerable persons affected by TB, namely migrants, and how the screening for TB infection is performed on an European level, in order to set the groundwork for future European consensus. Overall, results of this thesis indicate that greater care should be offered to persons at risk of developing side effects of TB or of the treatment for TB and more research should be involved in implementing personalised medicine techniques at all levels of the clinical care cascade.<br/

Traces of Radioactive I-131 in Rain Water and Milk Samples in Romania

Measurements of I-131 (T1/2 = 8.04 days) have been performed in IFIN-HH's underground laboratory situated in Unirea salt mine from Slanic-Prahova, Romania. The rain water samples were collected in March 27th in Brasov and in March 27th, 29th and April 2nd in Slanic. Also sheep milk was collected in Slanic area and subsequently measured. The samples were measured in the IFIN-HH's underground laboratory in ultra-low radiation background, using a high resolution gamma-ray spectrometer equipped with a GeHP detector having a FWHM = 1.80 keV at 1332.48 keV at the second Co-60 gamma-ray, and a relative efficiency of 22.8%. The results show a specific activity of I-131 from 0.17 to 0.87 Bq/dm^3. In the sheep milk from Slanic area the specific activity of I-131 was about 6 Bq/dm^

Application of 137 Cs for measuring soil erosion/deposition rates in Romania

Two methods of monitoring soil redistribution along agroterraces were explored in Tarina basin of the Moldavian Plateau: the classical method of annual or periodic field measurements and the 137C technique. Results obtained by both methods indicate that the aggradation rate of the agroterrace edge averages 5.0-6.0 cm/yr, but the 137C technique is more efficient because it requires only one field visit. Much of the dow n ward movement of soil in these agroterraces can be related to contour ploughing, although some erosion/deposition undoubtedly occurs. The future of using 137C as a tracer of erosion and sedimentation within discontinuous gullies is promising. Some results obtained in the Moldavian Plateau near Barlad support this assumption. A field study, based on a depth - incremental sampling method, was undertaken in two small basins, Roscani and Timbru. Depth distribution of 137Cs from recent sediments deposited along the floor of dis-continuous gullies allowed the establishment of a mean sedimentation rate of 4.4 cm/yr over the period 1963-1996, and 2.5 cm/yr after 1986 for short gullies. In the case of long gullies, after the Chernobyl nuclear accident this value is to 4.9 cm/year. Furthermore, it was possible to estimate: the age of the gullies (23-48 years), the mean gully head advance (0.9 m/yr), the mean total mass of sediment deposited/ eroded within the gully system (up to 124 t/yr) and the main sediment source (the active gully head and banks). Conservation practices and tillage were first implemented during 1982-1983 in the upper Racatau basin of 3,912 hectares. Significant changes in land management practices resulted from the application of the Landed Property Law no.18/1991. The marked shifting from contour to up and down hill farming created a doubling in the amount of soil erosion and deposition. Depth distribution of 137Cs in recent sediments of the Bibiresti reservoir indicates a mean sedimentation rate of 5.0 cm/yr over the period 1986-1992 and 10.0 cm/yr for the period 1993-1996

Assessment of the reservoir sedimentation rates from 137 Cs measurements in the Moldavian Plateau

Reservoir sedimentation has been recognized as an important environmental threat in the Moldavian Plateau of Eastern Romania. Measurements of the 137Cs content of reservoir and, sometimes, floodplain sediments have been used to estimate the rate of sedimentation over the past 13-36 years . The estimated mean sediment accumulation rates in the reservoirs from three geomorphological subunits vary between 2.6 and 7.9 cm/year with an average rate of 4.6 cm/year after April 1986. Strong relationships were established between the individual sedimentation rates and the drainage area within the southern and central part of the Moldavian Plateau. The shape of the 137Cs depth profile was used as the main approach. Taking into account that the standard pattern is in the form of a cantilever and based on burial magnitude of 137Cs peak derived from Chernobyl two chief patterns of reservoir sedimentation were identified, shallow and deep buried cantilever, respectively

Brivaracetam inhibits spreading depression in rat neocortical slices in vitro

AbstractEpilepsy and migraine are episodic neurological disorders with marked co-morbidity, making migraine common among epileptic patients. Conversely, several antiepileptic drugs (AEDs) are used as migraine-preventive medication. Cortical spreading depression (CSD) represents a transient suppression of bioelectric activity and is considered a key event in migraine and stroke. This study assessed the novel AED candidate brivaracetam (BRV) vs. the chemically related AED levetiracetam in a rat neocortical slice model allowing consistent quantification of drug effects on CSD. CSD episodes were regularly elicited on slices upon delivery of calibrated KCl drops and were recorded via two micropipette electrodes. After control CSDs, the drug was added to the perfusion and five subsequent CSDs were elicited during drug perfusion. Effects were assessed via CSD amplitude (Ampl) and duration at half-amplitude (D1/2). BRV, 10 and 32μM reduced the Ampl and transiently the D1/2. Levetiracetam, 32 and 100μM had no effect on either Ampl or D1/2. The anti-CSD effect of BRV in this in vitro model might suggest a potential anti-migraine activity of this compound, which warrants further investigation

Assessment of the reservoir sedimentation rates from 137 Cs measurements in the Moldavian Plateau

Reservoir sedimentation has been recognized as an important environmental threat in the Moldavian Plateau of Eastern Romania. Measurements of the 137Cs content of reservoir and, sometimes, floodplain sediments have been used to estimate the rate of sedimentation over the past 13-36 years . The estimated mean sediment accumulation rates in the reservoirs from three geomorphological subunits vary between 2.6 and 7.9 cm/year with an average rate of 4.6 cm/year after April 1986. Strong relationships were established between the individual sedimentation rates and the drainage area within the southern and central part of the Moldavian Plateau. The shape of the 137Cs depth profile was used as the main approach. Taking into account that the standard pattern is in the form of a cantilever and based on burial magnitude of 137Cs peak derived from Chernobyl two chief patterns of reservoir sedimentation were identified, shallow and deep buried cantilever, respectively

Institutional adaptation in environmental domain: the case of Moldova

Environment currently, more than ever, receives high attention as (for example) scandalous cases of disturbed ecosystem due to negligent waste management system are widely distributed through media and social channels. Even if we are making abstraction of social activists that protest against, as they claim, climate change, it is true that most governments acknowledge the pressure to introduce new measures and tools for tackling environmental issues with its broad spectrum of sub-domains

Genetic mechanisms of drug resistance in cancer chemotherapy

Department of Molecular biology and Human genetics, Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova, The 8th International Medical Congress for Students and Young Doctors, September 24-26, 2020Introduction. One of the major problems in cancer chemotherapy is the development of drug resistance during treatment. Currently, 90% of failures in chemotherapy are during the invasion and metastasis of cancers related to drug resistance that can develop in different mechanisms.Aim of the study. To study genetic mechanisms of drug resistance in cancer chemotherapy. Materials and methods.: This paper is a descriptive research, based on retrospective analysis. Analysis of statistical data, current management documents, reports, studies, bibliographic and digital sources have been carried out with reference to the topic. Results. The study of the genetic mechanisms of drug resistance in the treatment of cancer has identified the presence of different extracellular and intracellular mechanisms: tumor heterogeneity, tumor microenvironment, cancer stem cells, inhibition of cell death, inactivation of anticancer drugs, multi-drug resistance (MDR), changing drug metabolism, changing chemotherapeutic agents targets, enhancing DNA repair, gene amplification, epigenetic changes, microRNA. Responsible for multiplication, growth and metastasis have been shown to be some genes that encode for kinases. According to the latest studies, use of kinase inhibitor preparations is effective in both stopping progression of cancer and increasing the intracellular concentration of the preparation in MDR cells. Conclusions. Cancer drug resistance is a complex phenomenon determined by numerous mechanisms and some genes. Gaining knowledge about these particularities and performing genetic tests make it possible to avoid the misuse of the preparations, in order to prevent the chemotoxicity on the organism and affect the systems with a high division rate

L-Lactate Regulates the Expression of Synaptic Plasticity and Neuroprotection Genes in Cortical Neurons: A Transcriptome Analysis.

Lactate, a product of aerobic glycolysis in astrocytes, is required for memory formation and consolidation, and has recently emerged as a signaling molecule for neurons and various cell types in peripheral tissues. In particular lactate stimulates mRNA expression of a few plasticity-related genes. Here, we describe a RNA-seq study that unravels genome-wide transcriptomic responses to this energy metabolite in cortical neurons. Our results show that mRNA expression of 20 immediate-early genes involved in the MAPK signaling pathway and in synaptic plasticity were increased by more than twofold following 1 h of lactate stimulation. This effect was dependent on NMDA receptor (NMDAR) activity since it was prevented by pre-treatment with MK-801. Comparison with published datasets showed that a significant proportion of genes modulated by lactate were similarly regulated by a stimulation protocol activating specifically synaptic NMDARs known to result in upregulation of pro-survival and downregulation of pro-death genes. Remarkably, transcriptional responses to lactate were reproduced by NADH (for 74 of the 113 genes, FDR &lt; 0.05), suggesting a redox-dependent mechanism of action. Longer-term gene expression changes observed after 6 h of lactate treatment affected genes involved in regulating neuronal excitability and genes coding for proteins localized at synapses. Gene set enrichment analyses performed with ranked lists of expressed genes revealed effects on molecular functions involved in epigenetic modulation, and on processes relevant to sleep physiology and behavioral phenotypes such as anxiety and hyperactivity. Overall, these results strengthen the notion that lactate effectively regulates activity-dependent and synaptic genes, and highlight new signaling effects of lactate in plasticity and neuroprotection

Oscillating policy focus between agriculture and protected areas within environmental lav in Republic of Moldova

У тезах доповіді автором порушена проблема правового регулювання діяльності у галузі сільськогосподарського виробництва в Республіці Молдова з урахуванням екологічних та кліматичних вимог, а також соціальних аспектів (урбанізації, міграції, робочої міграції)Elena Marginean